Background and Aims: The association of superficial thrombophlebitis (ST) with deep-venous thrombosis varies between 6% and 44%. Thus, prevention of ST is important. The aim of this study was to compare the efficacy of topical quick penetrating solution (QPS) of heparin 1000 IU/mL versus diclofenac QPS for prevention of postinfusion ST. Settings and Design: This is a randomized, controlled, double-blind study. Materials and Methods: The study was done after ethical clearance and Clinical Trial Registry- India registration to compare 100 patients for the prevention of ST with application of heparin QPS and diclofenac QPS at regular intervals. Patients were randomized into two groups (Group H [control group] – heparin QPS group and Group D – diclofenac QPS group) and the assigned treatment was applied four times daily. The appearance of thrombophlebitis was graded on the basis of infusion nursing society scale. The site of venous cannulation was inspected every 6 h for any changes for the next 5 days. Statistical Analysis: The parametric data were analyzed using Student's t-test and nonparametric data were analyzed by Kruskal–Wallis test. Results: Of 98, only 10 patients developed thrombophlebitis and all belonged to Group D (23%). No patient belonging to Group H developed thrombophlebitis (0%). This difference was statistically significant (P = 0.034). Conclusion: The QPS formulation of heparine and diclofenac was effective in preventing thrombophlebitis. Heparine QPS is more effective than diclofenac QPS for the same.

The most common procedure done in hospitalized patients worldwide is securement of a peripheral intravenous cannula (PIVC). The most frequent complication of PIVC is superficial thrombophlebitis (ST).[1] The incidence of phlebitis varies from 5% to 70% in different studies.[2],[3] This wide variation in incidence may be attributed in part to the absence of a universally accepted scale with strong demonstrated reliability and the other reason may be due to lack of standard diagnostic criteria for determining and defining phlebitis. Once this phlebitis develops, it will not only bring cascade of unwanted complications such as pain, induration, and edema but can also lead to serious complications such as deep-vein thrombophlebitis.[2] In view of serious complications associated with it, prophylaxis should be better than treatment in managing patients with PIVC. Numerous published studies have used low-dose unfractionated heparin and low-molecular-weight heparin intravenously or topical application of heparin for treatment of this thrombophlebitis after its appearance.[4],[5] One recent study has used topical heparin as prophylaxis for prevention of appearance of ST on PIVC.[6] Quick penetrating solution (QPS) technology enables an effective drug delivery through the stratum corneum and it has ease of administration. The aim of the present study was to compare the efficacy of heparin or diclofenac in QPS formulation for prevention of ST.

Materials and Methods

The present study is randomized, controlled, double-blind study conducted in our tertiary center after taking clearance from the Institutional Ethical Committee. The clinical trial is also registered with Clinical Trial Registry- India (CTRI/2017/10/010153). A total of 100 patients posted in operation theater or admitted in the intensive care unit requiring a venous cannulation for ≥72 h between January 2018 and April 2018 belonging to the American Society of Anesthesiologists' (ASA) physical Status (I, II, III) aged 20–60 years were selected for the study. Patients not giving consent, with known hypersensitivity to heparin or diclofenac, coagulation disorders, or anticoagulants were not included in the study. Patients were randomly allocated into two groups using a computer-generated random number table.

Group H (control group) – patients who received topical heparin (1000 IU/mL) 6 hourly – and Group D – patients who received topical diclofenac 6 hourly. Area of cannulation was cleaned with surgical spirit and an 18-G cannula (B Braun Vasofix) was inserted using aseptic precaution. After insertion of the cannula, before securing the cannula topical heparin 1000 IU/mL (Phlebotroy QPS, Troikaa Pharmaceuticals) or diclofenac QPS (Dynapar QPS, Troikaa Pharmaceuticals) 10 drops according to assigned group was applied and that time was marked as “0” hour. Patients and investigator both were blinded for the type of QPS drop being used. The QPS bottle was covered by opaque plain paper marked A or B. The nursing staff not involved in the study had randomization list of patient with instruction to give drug A or B. Every 6 h, the same site was examined and scored using infusion nursing society (INS) phlebitis score,[7] the current version (0, no symptoms; 1, pain and erythema; 2, pain, erythema, and edema; 3, pain, erythema, edema, and streak formation; 4, pain, erythema, edema, streak formation, and palpable venous cord >2.54 cm in the length and purulent discharge) and again the 10 drops was applied by the nursing staff, and the site was covered with adhesive tape for next 6 h. Any score of 1 or greater was considered phlebitis. This regime was followed for 120 h. Any adverse effect if present was noted. The sample size calculation was performed using software, PS Power and Sample Size Calculations Program, Version No. 3 (Kayesville, Utah, USA). Based on the study,[6] a sample size of 90 patients, 45 in each arm, is required to detect a clinically significant difference of 20% between groups in proportion of patients developing thrombophlebitis using a two-tailed Chi-square test with 80% power and a 5% level of significance. Considering dropout, a total of 100 patients (50 patients in each group) were to be included in the study. Quantitative data are presented as mean ± standard deviation, whereas categorical data are expressed as absolute number/proportion of patients. Quantitative data of both the treatments groups were analyzed by unpaired t-test or Mann–Whitney test based on the distribution of data. Chi-square test or Fisher exact test was used to compare the categorical data of both the treatment groups. P < 0.05 was considered as statistically significant difference between both the treatment groups. All statistical analyses were performed using software, Graph Pad prism, version 5 (California, USA).

Results

A total of 100 patients were enrolled for the study, of which two patients could not finish the study because cannula was removed as a result of early discharge as we can see in the consort diagram [Table 1]. The demographic data of both the group were comparable in age, sex, ASA grading, size of cannula, site of cannula, and duration of cannulation.

Of 98 patients, only ten patients developed Grade 1 thrombophlebitis and all belonged to Group D (23%). No patient belonging to Group H developed thrombophlebitis (0%). This difference was statistically significant (P = 0.034) [Table 2].

Table 2: Comparison of development of thrombophlebitis in both the group

Thrombophlebitis is the most common complication of intravenous (IV) catheter and can lead to many problems and multiple cannulation. We used topical QPS formulation of heparin and diclofenac for prevention of appearance of this formulation. Heparin QPS was found to be 100% effective in preventing the appearance of thrombophlebitis. Diclofenac QPS, the other drug used by us, was also effective but less than heparin QPS and thus may be used when use of heparin is contraindicated.

It is now established that the etiology of thrombophlebitis is multiple.[2] There are three different types of phlebitis mechanical, chemical and infectious, and multiple risk factors for development of all the three types of phlebitis.[2] Mechanical phlebitis occurs when a peripheral IV catheter is not secured properly, leading the catheter to change position within the vein. Chemical phlebitis is caused by highly vesicant irritants such as drugs.[7],[8] Infectious or bacterial phlebitis is caused when an infectious agent is introduced into the peripheral IV catheter. Infectious phlebitis can be caused by contamination of the catheter tip anytime during IV insertion.[7] It may also occur if a cannula is left in place longer than recommended by the Centers for Disease Control and Prevention (CDC). The CDC recommends rotating the IV cannula every 72–96 h to reduce the risk of infection and patient discomfort associated with phlebitis. There are a huge number of patients who need IV cannulation for a long period of time, and rotation of cannula not only increases morbidity in the patients but also increases undue monetary burden in the patients. Thus, we should concentrate on the prevention of appearance of this TP.

In the United States, the INS currently recommends using either the INS tool, as evaluated by Groll et al., or the visual infusion phlebitis scale, as per Gallant and Schultz for grading thrombophlebitis.[9] We have used the modified INS phlebitis scale for the purpose of identification and measurement of phlebitis; the instructions are clear and the scale is easy and fast and clinically appropriate. The INS scale has changed over time, with the current version being the progressive score from 0 (no symptom) to 4 (pain at access site with erythema and/or edema, streak formation, palpable venous cord >1 in length; purulent drainage).

Belcaro et al. studied the effect of topical formulation of heparin (heparin gel) in reducing the symptoms of superficial venous thrombosis and found it remarkable in reducing pain, erythema, and edema. In the study, both investigators and patients global assessment of efficacy were significantly better with heparin gel. No adverse events or reactions were reported during the study and follow-up period with the application of heparin gel.[4] In another study, heparin QPS formulation was used and was found to be more effective in the treatment of postinfusion ST with similar safety profile to heparin gel.[10] Hands-free usage of heparin QPS would facilitate ease of application and improve compliance of patients as well as nursing staff. Thus, in our study, we used heparin QPS and compared its efficacy with diclofenac QPS. Since we used the drug prophylactically before the appearance of the thrombophlebitis, we got excellent results in only 10.02% patient presenting with Grade 1 phlebitis. All patients who developed Grade 1 phlebitis were in diclofenac group, thus establishing the fact that topical heparin is better in preventing appearance of phlebitis post venous cannulation. Diclofenac QPS can also be used for prevention of thrombophlebitis developed due to venous cannulation, but it is inferior to the heparin QPS. It can be used in patients allergic to heparin preparation or in patients in whom use of heparin should be avoided.

The limitation of this study was that we used heparin QPS as control group; thus incidence of appearance phlebitis without any prophylaxis cannot be estimated. The other limitation of the study was smaller sample size. A future study can be planned with a bigger sample size to establish our obtained results.

Conclusion

The QPS formulation of heparine and diclofenac was effective in preventing thrombophlebitis. Heparine QPS is more effective than diclofenac QPS for the same. If patients have any contraindication for the use of heparine QPS then diclofenac QPS can be used as an alternative.